INCREASED EXPRESSION OF TYRO3 AND PROTEIN S IN CIRCULATING CD11b+ CELLS OF PATIENTS WITH ACTIVE LANGERHANS CELL HISTIOCYTOSISBackground: TYRO3, AXL and MERTK (TAM) tyrosine kinase receptors and its cognate agonist Protein S (PROS1) have been identified as

TESSONE LICINA; NOWAK WANDA; ESTECHO IVANA G; ARMESTO ARNALDO R; ELENA GRACIELA; ROTHLIN CARLA V; CARRERA SILVA EUGENIO A; ROSSO DIEGO A; ERRASTI ANDREA E

Mar del Plata

Congreso; Reunión Conjunta SAIC-SAI-SAFE 2016; 2016

SAIC-SAI-SAFE

<!-- /* Font Definitions */@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536859905 -1073711037 9 0 511 0;}@font-face{font-family:"ＭＳ 明朝";mso-font-charset:78;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1791491579 18 0 131231 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1073743103 0 0 415 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0in;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}@page WordSection1{size:8.5in 11.0in;margin:1.0in 1.25in 1.0in 1.25in;mso-header-margin:.5in;mso-footer-margin:.5in;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->Background:TYRO3, AXL and MERTK (TAM) tyrosine kinase receptors and its cognate agonistProtein S (PROS1) have been identified as negative regulators of the immuneresponse as well as non-classical proto-oncogenes, aberrantly expressed inmultiple haematological and epithelial malignancies. Langerhans Cell (LC) Histiocytosis(LCH) is a disorder characterized by an abnormal accumulation of CD207+CD1a+myeloid cells in almost any tissue. The etiology of this disease is still underscientific discussion and it is not clear if LCH results from malignanttransformation or unbalanced immune response that leads to the proliferation ofpathogenic LC-like cells. Our aim is to explore the role of the TAM axis in thepathogenesis of pediatric LCH. Methods:We analyzed the expression of TAM receptors and PROS1 in peripheral blood mononuclearcells of pediatric patients with confirmed diagnosis of LCH stratified asunisystem or multisystem with active disease (AD) or non-active disease (NAD) andadult controls. The expression levels of PROS1 and TAM receptors weredetermined by flow citometry and expressed as fold increase of meanfluorescence intensity (MFI) compared to the isotype control. Results: Circulating total CD11b+fraction was significantly expanded in AD (36.4 ± 3.7 % N=11) vs NAD (18.9 ±1.7 % N=12) and adult controls (24.9 ± 1.3 % N=12). Interestingly, thisfraction that is consider the main source of inflammatory myeloid cells, showedhigher levels of PROS1 in AD (14.2-fold N=4) compared with NAD (6-fold N=5) andadult controls (6.7-fold N=6). TYRO3 was also up regulated in circulatingCD11b+ cells in AD (10.6-fold N=8) compared with NAD (5-fold N=9) and adultcontrols (4.5-fold N=6). Conclusion:Our results show that higher levels of TYRO3 and PROS1 are associated with activeand multisystem LCH suggesting that this axis could be involved in the expansionof precursor and pathological LC-like cells.